Erratum: Stromal–epithelial crosstalk regulates kidney progenitor cell differentiation

Das, Aditi; Tanigawa, Shunsuke; Karner, Courtney M.; Xin, Mei; Lum, Lawrence; Chen, Chuo; Olson, Eric N.; Perantoni, Alan O.; Carroll, Thomas J.

doi:10.1038/ncb2853

Cited by 3 publications

(1 citation statement)

References 26 publications

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“…Cells were also probed for YAP1 by IF and observed to express this tumor marker in cultured tumor cell nuclei as well ( Figure 3E ). This observation corresponds with the staining pattern in fixed tumor tissues ( Figure 2 and prior report ( 34 ) and is consistent with YAP activation in tumor cells ( 43 , 44 ).…”

Section: Resultssupporting

confidence: 92%

Exploiting embryonic niche conditions to grow Wilms tumor blastema in culture

Wojcik

Lovvorn²,

Hollingshead³

et al. 2023

Front. Oncol.

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IntroductionWilms Tumor (WT), or nephroblastoma, is the most common pediatric kidney cancer. Most WTs display a “favorable” triphasic histology, in which the tumor is comprised of blastemal, stromal, and epithelial cell types. Blastemal predominance after neoadjuvant chemotherapy or diffuse anaplasia (“unfavorable” histology; 5-8%) portend a worse prognosis. Blastema likely provide the putative cancer stem cells (CSCs), which retain molecular and histologic features characteristic of nephron progenitor cells (NPCs), within WTs. NPCs arise in the metanephric mesenchyme (MM) and populate the cap mesenchyme (CM) in the developing kidney. WT blastemal cells, like NPCs, similarly express markers, SIX2 and CITED1. Tumor xenotransplantation is currently the only dependable method to propagate tumor tissue for research or therapeutic screening, since efforts to culture tumors in vitro as monolayers have invariably failed. Therefore, a critical need exists to propagate WT stem cells rapidly and efficiently for high-throughput, real-time drug screening.MethodsPreviously, our lab developed niche conditions that support the propagation of murine NPCs in culture. Applying similar conditions to WTs, we assessed our ability to maintain key NPC "stemness" markers, SIX2, NCAM, and YAP1, and CSC marker ALDHI in cells from five distinct untreated patient tumors.ResultsAccordingly, our culture conditions maintained the expression of these markers in cultured WT cells through multiple passages of rapidly dividing cells.DiscussionThese findings suggest that our culture conditions sustain the WT blastemal population, as previously shown for normal NPCs. As a result, we have developed new WT cell lines and a multi-passage in vitro model for studying the blastemal lineage/CSCs in WTs. Furthermore, this system supports growth of heterogeneous WT cells, upon which potential drug therapies could be tested for efficacy and resistance.

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Section: Resultssupporting

confidence: 92%

Exploiting embryonic niche conditions to grow Wilms tumor blastema in culture

Wojcik

Lovvorn²,

Hollingshead³

et al. 2023

Front. Oncol.

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β-Catenin Overexpression in the Metanephric Mesenchyme Leads to Renal Dysplasia Genesis via Cell-Autonomous and Non–Cell-Autonomous Mechanisms

Sarin

Boivin

et al. 2014

The American Journal of Pathology

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Renal dysplasia, a developmental disorder characterized by defective ureteric branching morphogenesis and nephrogenesis, ranks as one of the major causes of renal failure among the pediatric population. Herein, we demonstrate that the levels of activated β-catenin are elevated in the nuclei of ureteric, stromal, and mesenchymal cells within dysplastic human kidney tissue. By using a conditional mouse model of mesenchymal β-catenin overexpression, we identify two novel signaling pathways mediated by β-catenin in the development of renal dysplasia. First, the overexpression of β-catenin within the metanephric mesenchyme leads to ectopic and disorganized branching morphogenesis caused by β-catenin directly binding Tcf/lef consensus binding sites in the Gdnf promoter and up-regulating Gdnf transcription. Second, β-catenin overexpression in the metanephric mesenchyme leads to elevated levels of transcriptionally active β-catenin in the ureteric epithelium. Interestingly, this increase of β-catenin-mediated transcription results from a novel Ret/β-catenin signaling pathway. Consistent with these findings, analysis of human dysplastic renal tissue demonstrates that undifferentiated mesenchymal cells expressing high levels of β-catenin also express increased GDNF. Furthermore, dysplastic ureteric tubules that were surrounded by high levels of GDNF also exhibited increased levels of activated β-catenin. Together, these data support a model in which the elevation of β-catenin in the metanephric mesenchyme results in cell-autonomous and non-cell-autonomous events that lead to the genesis of renal dysplasia.

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Exploiting Embryonic Niche Conditions to Grow Wilms Tumor Blastema in Culture

Wojcik

Lovvorn

Hollingshead

et al. 2022

Preprint

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Wilms Tumor (WT), or nephroblastoma, is the most common pediatric kidney cancer. Most WTs display a favorable triphasic histology, in which the tumor is comprised of blastemal, stromal, and epithelial cell types. Blastemal predominance after neoadjuvant chemotherapy or diffuse anaplasia (unfavorable histology; 5-8%) portend a worse prognosis. Blastema likely provide the putative cancer stem cells (CSCs), which retain molecular and histologic features characteristic of nephron progenitor cells (NPCs), within WTs. NPCs arise in the metanephric mesenchyme (MM) and populate the cap mesenchyme (CM) in the developing kidney. WT blastemal cells, like NPCs, similarly express markers, SIX2 and CITED1. Tumor xenotransplantation is currently the only dependable method to propagate tumor tissue for research or therapeutic screening, since efforts to culture tumors in vitro as monolayers have invariably failed. Therefore, a critical need exists to propagate WT stem cells rapidly and efficiently for high-throughput, real-time drug screening. Previously, our lab developed niche conditions that support the propagation of murine NPCs in culture. By applying similar conditions to WTs, we have successfully expanded and passaged WT cells from five distinct untreated patient tumors and maintained key NPC stemness markers, SIX2, NCAM and YAP1, and CSC marker ALDH1. These findings suggest that our culture conditions sustain the WT blastemal population, as previously shown for normal NPCs. As a result, we have developed new WT cell lines and a multi-passage in vitro model for studying the blastemal lineage/CSCs in WTs. Furthermore, this system supports growth of heterogeneous WT cells, upon which potential drug therapies could be tested for efficacy and resistance.

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Erratum: Stromal–epithelial crosstalk regulates kidney progenitor cell differentiation

Cited by 3 publications

References 26 publications

Exploiting embryonic niche conditions to grow Wilms tumor blastema in culture

Exploiting embryonic niche conditions to grow Wilms tumor blastema in culture

β-Catenin Overexpression in the Metanephric Mesenchyme Leads to Renal Dysplasia Genesis via Cell-Autonomous and Non–Cell-Autonomous Mechanisms

Exploiting Embryonic Niche Conditions to Grow Wilms Tumor Blastema in Culture

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